This in vitro study of drug-radiation interactions will use low ET radiation and four nitrosourea analogs with distinct chemical activities: BCNU, ENU, chlorozotocin, and BHCNU. Because of the variety of lesions in mammalian cells, these drugs should interact with radiation in demonstrably different ways. Using the 9L monolayer system, we propose to identify combinations of drug and radiation that interact, as detected by cell survival, sister chromatin exchange, and alkaline elution. An attempt will be made to explain these interactions on the basis of lesion type, cell cycle age response, inhibition of recovery, cell cycle perturbations, and pharmacokinetics. We hope to uncover the causative factors underlying nitrosourea-radiation interactions so that clinical protocols based on interactions of this important class of anticancer drugs can be proposed with a reasonable probability of success.